Resistance mechanisms of tumor stem cells
Cancer is one of the major diseases which pose a threat to human health in modern. Currently the main treatments for cancer are surgery, radiotherapy, chemotherapy and biological therapy et al. In the treatment of tumors, the drugs can often inhibit the tumor growth by inducing tumor cell apoptosis or inhibiting proliferation. But because of the existence of cancer stem cells, it is often difficult for the drug to remove all tumor cells.
Tumor stem cells (TSCs), also called cancer stem cells (CSCs) or tumor-initiating cells (TICs), is a small portion of tumor cells, which are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. CSCs produce some proteins, which could increase their resistance towards chemotherapeutic agents.
Resistance mechanisms of cancer stem cells are very complex, we summarized it in general as follows 8 aspects:
- Drug efflux
- Abnormal anti-apoptotic pathway leads to the raise of anti-apoptotic ability
- Differentiation
- Aldehyde dehydrogenase
- The increase of DNA damage repair capacity
- Increased antioxidant capacity lead to Vivo redox imbalance
- CSCs have strict cell cycle or in quiescent phase
- Pro-survival signaling pathways
From 1980 to 2012, the obesity incidences of United States were raised linearly, and the mortality rate caused by obesity also increased with age.
Liraglutide, a GLP-1 receptor agonist developed by Novo Nordisk has been approved by EMA in 2009 and by FDA in 2010 for the treatment of type II diabetes.
Liraglutide could stimulates insulin secretion in a glucose concentration-dependent manner, it also increase the number of pancreatic? cells, reduce the fasting blood glucose, postprandial blood glucose and HbA1c. In addition, liraglutide can act on the central nervous system (especially the hypothalamus) and make the body feel satiety and and lose the interest in eating. Furthermore, liraglutide also inhibit gastrointestinal motility and gastric secretion, which helps to delay gastric emptying contents and reduce the food intake.
The LEAD series of studies confirmed that liraglutide can reduce the average weight of type 2 diabetes patients for about 2~3 kg with no side effects such as significant nausea, vomiting, diarrhea and other symptoms. The "Lancet" article of Astrup A indicated that liraglutide could reduce the weight of Obesity type 2 diabetes mellitus patients compared with orlistat. In addition to weight loss, the liraglutide also has a significant role in blood pressure, lipid, liver protection and other aspects.
Combining the multi-advantages of liraglutide, it could become the stars of the future. Liraglutide, currently being studied as a weight loss medication, is waiting for FDA approval with another weight loss drug-bupropion/ naltrexone.